Role of erythropoietin in the brain

Crit Rev Oncol Hematol. 2007 Nov;64(2):159-71. doi: 10.1016/j.critrevonc.2007.03.001. Epub 2007 May 4.


Multi-tissue erythropoietin receptor (EPO-R) expression provides for erythropoietin (EPO) activity beyond its known regulation of red blood cell production. This review highlights the role of EPO and EPO-R in brain development and neuroprotection. EPO-R brain expression includes neural progenitor cells (NPC), neurons, glial cells and endothelial cells. EPO is produced in brain in a hypoxia sensitive manner, stimulates NPC proliferation and differentiation, and neuron survival, and contributes to ischemic preconditioning. Mice lacking EPO or EPO-R exhibit increased neural cell apoptosis during development before embryonic death due to severe anemia. EPO administration provides neural protection in animal models of brain ischemia and trauma, reducing the extent of injury and damage. Intrinsic EPO production in brain and EPO stimulation of endothelial cells contribute to neuroprotection and these are of particular importance since only low levels of EPO appear to cross the blood-brain barrier when administered at high dose intravenously. The therapeutic potential of EPO for brain ischemia/trauma and neurodegenerative diseases has shown promise in early clinical trial and awaits further validation.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain Chemistry*
  • Endothelial Cells / chemistry
  • Endothelial Cells / cytology
  • Erythropoietin / physiology*
  • Erythropoietin / therapeutic use
  • Humans
  • Mice
  • Neurons / chemistry
  • Neurons / cytology
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Receptors, Erythropoietin / genetics
  • Receptors, Erythropoietin / physiology*
  • Stem Cells / cytology
  • Stem Cells / drug effects


  • Neuroprotective Agents
  • Receptors, Erythropoietin
  • Erythropoietin